Typhoid fever remains a serious cause of morbidity and mortality throughout under-developed nations. The immunopathogenic role of the capsular polysaccharide of S. typhi, the causative agent of typhoid, is controversial. There is much indirect evidence that serum Vi antibodies could exert protein against typhoid fever. Typhoid is only a disease of humans; there is no satisfactory animal model. Collaborative studies with Dr. H. Koornhof, South African Institute of Medical Research, I.L. Acharya, Infections Diseases Hospital, Kathmandu, Nepal and Dr. Ramesh Kumar, All India Institute of Medical Sciences have been established to study the prevalence of Vi antibodies in the population, the age-specific attack rate and the ultimately effectiveness of Vi polysaccharide vaccines in these various areas. The Vi polysaccharide has been purified and derivatized with tyramine for use as a 125I antigen. The technique for preparing the tyramine derivatives and purification of the Vi is being prepared for publication. A clinical study of the Vi polysaccharide, prepared in our laboratory in 1974 BB-IND 660 was done in collaboration with Dr. Myrone Levine, University of Maryland. This Vi preparation passed the current FDA guidelines for pyrogen content of meningococcal capasular polysaccharide vaccines. However, when administered by jet gun, one of 24 volunteers developed 102 degrees C. In addition to Vi antibodies, O-specific antibodies were elicited in the volunteers. Accordingly, the high specific activity of S. typhi LPS and the effect of the jet gun upon immediate reactivity necessitates that Vi products of higher purity be prepared.